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Biomedical subjects

A Choudhury

Publications and source records attributed to A Choudhury.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alternate splicing at the 3'-end of the human pancreatic tumor-associated mucin MUC4 cDNA.

MUC4 is a membrane-bound mucin and is considered as the human homologue of the rat sialomucin complex (SMC). The deduced structural organization of the wild type-MUC4 cDNA (WT-MUC4) sequence revealed two subunits: a large amino mucin type subunit (MUC4alpha) and a transmembrane subunit (MUC4beta). MUC4beta is a membrane-bound growth factor like subunit and contains three EGF-like domains. The MUC4 gene is expressed in several normal tissues like trachea, lung, and testis. It is not expressed in a normal human pancreas; however, its dysregulation results in high levels of expression in pancreatic tumors and tumor cell lines. Recently, we have demonstrated the presence of alternative splice events in the 3'-end of the MUC4 cDNA that generated new putative variants (sv1-sv10) in normal human testis and in a pancreatic tumor cell line (HPAF). In search of MUC4 variant(s) that are specific to pancreatic adenocarcinoma, we investigated the splicing phenomena in the MUC4 cDNA sequence by using a large panel of pancreatic tumor cell lines. We have identified ten alternative splice events located downstream to the central large tandem repeat domain. These splice events generated 12 variant species (sv4, sv9, sv10-18, and sv21) of MUC4 cDNAs. The deduced amino acid sequence of these variant MUC4 cDNAs revealed two distinct types: a family of secreted and a membrane-associated variant form. Among the members of MUC4 secreted variant family, three (sv4, sv12, and sv13) of ten showed a short 144 residue COOH-terminus compared to 1154 residues in WT-MUC4. The variants with this short COOH-terminus (144 residues) was found in 37% (4/11) of the tumor lines. The putative membrane-bound variant sv10 was detected in 37% (4/11) pancreatic tumor cell lines but not in any normal human tissues. In conclusion, we have identified novel splice variant(s) of MUC4 in pancreatic adenocarcinoma.

3' Untranslated Regions↗
PubMed2001

Histopathology of Trypanosoma (Trypanozoon) evansi infection in bandicoot rat. I. visceral organs.

Experimental infection of Trypanosoma (Trypanozoon) evansi in Bandicota bengalensis produces an acute disease course leading to untimely death of the bandicoot rat. The sequential alteration of liver, spleen, lung, kidney, and heart was studied on the 5th, 8th, 12th, and 14th days postinoculation. The rats showed inflammatory, degenerative, and necrotic changes in these organs. In liver, pseudolobule formation, necrosis and hemorrhage within the sinusoids, and fatty degeneration of hepatic cells were the predominant histopathological changes. The changes were destructive and irreversible. In spleen giant cells aggregation and granulomatous lesion, i.e., accumulation of histiocytes, were the protective changes, whereas tissue and cell damage indicated irreversible degeneration. The gradual development of intrabronchus inflammation, aggregation of inflammatory cells around the alveoli, congestion of bronchioles, septal edema, atrophy of alveolar walls, migration of macrophages, and emphysema were the histopathological changes noticed in the lungs of the infected rats. The affected kidney showed infiltration of lymphocytes, hemorrhage in the interlobular space, and glomerulitis as the irreversible and destructive changes in the rats. There was degeneration of myocardium in the hearts of the rats. The histopathological changes in these organs are compared with those studied in surra, human sleeping sickness disease, and African trypanosomiasis. Possible mechanisms for these histological changes in the visceral organs are discussed.

Animals↗
PubMed2001

Aufbau principle of complex open-framework structures of metal phosphates with different dimensionalities.

Open-framework metal phosphates occur as one-dimensional (1D) chains or ladders, two-dimensional (2D) layers, and complex three-dimensional (3D) structures. Zero-dimensional monomers have also been isolated recently. These materials are traditionally prepared by hydrothermal means, in the presence of organic amines, but the reactions of amine phosphates with metal ions provide a facile route for the synthesis, and also throw some light on the mode of formation of these fascinating architectures. Careful studies of the transformations of monophasic zinc phosphates of well-characterized structures show that the 1D structures transform to 2D and 3D structures, while the 2D structures transform to 3D structures. The zero-dimensional monomers transform to 1D, 2D, and 3D structures. There is reason to believe that the 0D monomers, comprising four-membered rings, are the most basic structural units of the open-framework phosphates and that after an optimal precursor state, such as the ladder structure, is formed, further building may occur spontaneously. Evidence for the occurrence of self-assembly in the formation of complex structures is provided by the presence of the structural features of the one-dimensional starting material in the final products. These observations constitute the beginning of our understanding of the building-up principle of such complex structures.

Models, Molecular↗
PubMed2001

Antiretroviral therapy for HIV-2 infected patients.

OBJECTIVES: To evaluate clinical and RNA load response to antiretroviral therapy amongst patients infected with HIV-2 and to study the development of drug resistance. METHODS: Seven HIV-2 seropositive patients were monitored with clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four subjects were genotyped and in vitro recovery of virus by co-cultivation with PBMCs and HVS T-cells was attempted. Viruses isolated from two subjects were assayed for phenotypic antiviral resistance. The main outcome measures were the relationship between disease stage, viral load, CD4 cell count, viral subtype and the clinical course of HIV-2 infection and the effect of combination antiretroviral therapy on disease progression, CD4 cell count, HIV-2 RNA viral load and drug resistance. RESULTS: The median time of follow-up was 3 years (range 0-8 years). Three patients had AIDS, and one had symptomatic disease. Of the four patients genotyped, three were infected with HIV-2 subtype B and one with subtype A. Viraemia was detectable only at CD4 counts of less than 300 x 10(6)/ml. Two patients with high viral loads failed to respond to antiretroviral therapy although their treatment may not have been optimal. One developed in vitro phenotypic antiviral resistance. The genotype of this patient's viral reverse transcriptase is being analysed. CONCLUSIONS: In contrast to HIV-1, HIV-2 RNA levels were often undetectable despite advanced disease and low CD4 cell counts. However, HIV-2 was clearly capable of causing CD4 cell depletion resulting in symptomatic disease. The principles of highly active antiretroviral therapy seem to apply to HIV-2 and suboptimal therapy may lead to drug resistance. The timing of therapy initiation, monitoring of response and the measurement of resistance remain unresolved issues and conclusions cannot be extrapolated from HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Synthons and design in metal phosphates and oxalates with open architectures.

We briefly describe the structures of open-framework metal phosphates with different dimensionalities, such as the one-dimensional linear-chain and ladder structures, two-dimensional layer structures and three-dimensional structures with channels. We demonstrate the role of the zero-dimensional four-membered ring monomer and of the one-dimensional ladder structure as the starting building units or synthons involved in the formation of the complex architectures. Thus, we show how the one-dimensional ladder structure transforms to two- and three-dimensional structures under mild conditions. The two-dimensional layer structures also transform to three-dimensional structures, while the zero-dimensional monomer transforms to layered and three-dimensional structures under ordinary reaction conditions. These transformations provide an insight into the possible pathways involved in the building up of the complex structures of metal phosphates. The isolation of amine phosphates during the hydrothermal synthesis of metal phosphates and also the facile reactions between amine phosphates and metal ions to yield a variety of open-framework materials have thrown light on the mechanism of formation and design of these structures. The existence of a hierarchy of open-framework metal oxalates and their ready formation by employing amine oxalates as intermediates provides additional support to the observations made earlier with regard to the phosphates.

Journal Article↗
PubMed2001

Dose-finding based on feasibility and toxicity in T-cell infusion trials.

A new modality for treatment of cancer involves the ex vivo growth of cancer-specific T-cells for subsequent infusion into the patient. The therapeutic aim is selective destruction of cancer cells by the activated infused cells. An important problem in the early phase of developing such a treatment is to determine a maximal tolerated dose (MTD) for use in a subsequent phase II clinical trial. Dose may be quantified by the number of cells infused per unit body weight, and determination of an MTD may be based on the probability of infusional toxicity as a function of dose. As in a phase I trial of a new chemotherapeutic agent, this may be done by treating successive cohorts of patients at different dose levels, with each new level chosen adaptively based on the toxicity data of the patients previously treated. Such a dose-finding strategy is inadequate in T-cell infusion trials because the number of cells grown ex vivo for a given patient may be insufficient for infusing the patient at the current targeted dose. To address this problem, we propose an algorithm for trial conduct that determines a feasible MTD based on the probabilities of both infusibility and toxicity as functions of dose. The method is illustrated by application to a dendritic cell activated lymphocyte infusion trial in the treatment of acute leukemia. A simulation study indicates that the proposed methodology is both safe and reliable.

Algorithms↗
PubMed2001

Spinitectus osorioi n. sp. (Nematoda: Cystidicolidae) from Chirostoma spp. (Osteichthyes: Atherinidae) in Lake Pátzcuaro, Michoacán, México.

Spinitectus osorioi (Nematoda: Cystidicolidae) is described from the freshwater atherinids Chirostoma estor and Chirostoma attenuatum from Lake Pátzcuaro in the Mesa Central, Michoacán State, México. This nematode is characterized by a conspicuous protuberance on the ventral surface of the distal end of the long spicule that distinguishes it from its congeners in North America and in the neotropics. In addition, the species can be readily distinguished from 4 of the 5 nominal species of North American freshwater Spinitectus by the absence of either a terminal barb or heel on the short spicule and from Spinitectus mexicanus by the spination. Previous records of Spinitectus carolini from Chirostoma spp. in México (Lakes Pátzcuaro and Zirahuén) refer to S. osorioi, and the species appears to be specific to Chirostoma spp. The geological history of the Mesa Central drainages and the historical biogeography of freshwater atherinids in this region suggest that the origin of S. osorioi may be associated with either the marine history of their hosts or with host-switching from more distantly related freshwater hosts after colonization of freshwater environments by atherinids.

Animals↗
PubMed2001

Therapeutic potential of leukemia-derived dendritic cells: preclinical and clinical progress.

Human leukemia-derived dendritic cells show potential as tools for therapy. Leukemic cells of patients with chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and chronic myelomonocytic leukemia (CMML) will all undergo substantial differentiation toward dendritic cells (DC) and may be used to drive autologous T cells to acquire anti-leukemic cytotoxicity. This article describes the use of these human leukemia-derived dendritic cells for stimulation of allogeneic donor lymphocytes and presents a clinical trial of autologous CML DC-stimulated lymphocytes.

Clinical Trials as Topic↗
PubMed2001

Diphyllobothriasis: update on human cases, foci, patterns and sources of human infections and future considerations.

Diphylobothriasis is a well documented disease of humans. On a world scale new infections are reported regularly, especially from Russia and parts of Japan. Globally, new species have been discovered and the etiology of the disease may be changing. Human infections appear to be in decline but it is not clear if the sources of infection are also in decline or if public health awareness has improved. In North America there has been a decline in human cases while in South America an increase in reports from fish, especially salmonids suggests high levels in these fish species. The history of human infections of Diphyllobothrium latum is primarily associated with the consumption of the northern circumpolar distributed pike and percids and is often considered a parasite of humans only. Indeed some researchers believe that D. latum was introduced to North America by northern European immigrants. The more benign human infections of D. dendriticum appears to be primarily associated with salmonids and coregonid fishes and fish eating birds. Although the early cases of diphyllobothriasis in the 1930s in North America came from fish originating in Lake Winnipeg, Manitoba, there was general belief that it was declining in fish populations and therefore of little significance to humans in the area. However, high levels of a plerocercoid in the flesh of walleyes and pike led to rejection of commercially harvested walleye and pike in Manitoba and northern Ontario, Canada, and a financial loss to Aboriginal fishers. D. latum is widely distributed in fishes of Manitoba and is infective to humans where it is not pathogenic and has a life span up to 4.5 years. The distribution and potential infection routes has not changed in a century and is still well established in natural hosts in the boreal regions of North America. Evidence is building for an old pre-European presence in North America, involving the Beringian land bridge and later involvement of susceptible hosts (northern European immigrants).

Animals↗
PubMed2000

Retinoic acid-dependent transforming growth factor-beta 2-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-alpha signaling pathway.

The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist as two subunits: a mucin type unit known as MUC4alpha and a growth factor-like transmembrane subunit, MUC4beta. The expression of MUC4 in normal human pancreas is not detectable, but it is highly expressed in pancreatic tumor cells. In the present study, we investigated the regulation of MUC4 expression in human pancreatic tumor cells CD18/HPAF, exhibiting a high level of MUC4 transcripts and protein. When these cells were adapted to grow in the serum-free medium (CD18/HPAF-SF), the MUC4 expression was undetectable. Among several serum constituents, all-trans-retinoic acid (RA) induced the expression of MUC4 transcripts in a concentration- and time-dependent manner. The RA-mediated increase in the level of the MUC4 transcript coincided with an increased expression of transforming growth factor-beta2 (TGF-beta2) transcript. The antagonist of the retinoic acid receptor (RAR)-alpha (Ro41-5253) abrogated the expression of MUC4 and TGF-beta2 induced by RA. The exogenous addition of TGF-beta2 also increased the MUC4 expression. The TGF-beta-neutralizing antibody blocked the RA-induced as well as TGF-beta2-mediated MUC4 expression. In conclusion, induction of MUC4 expression in pancreatic carcinoma by RA is mediated through the RAR-alpha signaling pathway, and TGF-beta2 may serve as an interim mediator of this regulated expression.

Humans↗
PubMed2000

Formation of one-, two-, and three-dimensional open-framework zinc phosphates in the presence of a tetramine.

Five new open-framework zinc phosphates, encompassing the entire hierarchy of open-framework structures, have been synthesized hydrothermally in the presence of triethylenetetramine. The structures include one-dimensional ladders, two-dimensional layers, and three-dimensional structures as well as a zinc phosphate where the amine acts as a ligand. [C6N4H22]0.5[Zn(HPO4)2] (I): monoclinic, space group P2(1)/c (no. 14), a = 5.2677(1) A, b = 13.3025(1) A, c = 14.7833(1) A, beta = 96.049 degrees, Z = 4. [C6N4H22]0.5[Zn2(HPO4)3] (II): triclinic, space group P1 (no. 2), a = 7.515(1) A, b = 8.2553(1) A, c = 12.911(1) A, alpha = 98.654(1) degrees, beta = 101.274(1) degrees, gamma = 115.791(1) degrees, Z = 2. [C6N4H22]0.5[Zn2P2O8] (III): triclinic, space group P1 (no. 2), a = 8.064(1) A, b = 8.457(1) A, c = 9.023(1) A, alpha = 111.9(1) degrees, beta = 108.0(1) degrees, gamma = 103.6(1) degrees, Z = 2. [C6N4H22]0.5[Zn3(PO4)2(HPO4)] (IV): triclinic, space group P1 (no. 2), a = 5.218(1) A, b = 8.780(1) A, c = 16.081(1) A, alpha = 89.3(1) degrees, beta = 83.5(1) degrees, gamma = 74.3(1) degrees, Z = 2. [C6N4H20]0.5[Zn4P4O16] (V): monoclinic, space group P2(1)/c (no. 14), a = 9.219(1) A, b = 15.239(1) A, c = 10.227(1) A, beta = 105.2(1), Z = 4. The structure of I is composed of ZnO4 and HPO4 tetrahedra, which are edge-shared to form four-membered rings, which, in turn, form a one-dimensional chain (ladder). In II, these ladders are fused into a layer. The structures of III and IV comprise networks of ZnO4 and PO4 tetrahedra forming three-dimensional architectures. In V, the amine molecule coordinates to the Zn and acts as a pillar supporting the zinc phosphate layers, which possess infinite Zn-O-Zn linkages. The 16-membered one-dimensional channel in IV and the ZnO3N pillar, along with infinite Zn-O-Zn linkages in V, are novel features. The structure of the open-framework zinc phosphates is found to depend sensitively on the relative concentrations of the amine and phosphoric acid, with high concentrations of the latter favoring structures with lower dimensions.

Journal Article↗
PubMed2000

Hybrid open-framework iron phosphate--oxalates demonstrating a dual role of the oxalate unit

New inorganic-organic hybrid open-framework materials of the phosphate-oxalate family, [Fe2(H2O)2-(HPO4)2(C2O4)].H2O (I), [Fe2(H2O)2-(HPO4)2(C2O4)].2H2O (II), [C3N2H12]-[Fe2(HPO4)2(C2O4)1.5]2 (III), and [C3N2OH12][Fe2(HPO4)2(C2O4)1.5]2 (IV) have been synthesized hydrothermally in the presence of structure-directing amines. The amine molecules are incorporated in III and IV, whereas I and II are devoid of them. The oxalate units act as a bridge between the layers in all the compounds. The layers in I and II are entirely inorganic, being formed by FeO6 and PO4 units, whereas in III and IV oxalate units constitute the inorganic layers and act as the bridge between these layers. Such a dual role of the oxalate unit is unique and noteworthy. The formation of two types of inorganic layers in I and II consisting of four-, six-, and eight-membered rings, indicates the interconversions between the various rings in the phosphate--oxalates to be facile. All the phosphate--oxalates show antiferromagnetic ordering at low temperatures.

Journal Article↗
PubMed2000

Three-dimensional open-framework cobalt(II) phosphates by novel routes.

Two new three-dimensional open-framework cobalt phosphates, [C2N2H10]2[Co4(PO4)4]H2O, I, and [C4N3H16]3-[Co6(PO4)5(HPO4)3]H2O, II, have been prepared by the reaction of amine phosphates with Co2+ salts. I could also be prepared by the reaction of the cobalt tris amine complex with H3PO4. The crystal data for I and II are as follows: phosphate I, orthorhombic, space group P2(1)2(1)2(1) (no. 19), a = 10.277 (1) A, b = 10.302 (1) A, c = 18.836 (1) A, V = 1994.2 (2) A3, Z = 4; phosphate II, monoclinic, space group P2(1)/c (No. 14), a = 31.950 (1) A, b = 8.360 (1) A, c = 15.920 (1) A, beta = 96.6 (1) degrees V = 4223.4 (2) A3, Z = 4. The structures of both I and II are constructed from alternating CoO4 and PO4 tetrahedra. The connectivity leads to the formation of eight-membered channels in all the crystallographic directions resembling the aluminosilicate zeolite, merlinoite in the case of I and to a rather large, one-dimensional 16-membered channel in II. Strong hydrogen-bond interactions involving the amine and framework oxygen are present in both I and II.

Journal Article↗
PubMed2000

Disruption of T cell tolerance to self-immunoglobulin causes polyclonal B cell stimulation followed by inactivation of responding autoreactive T cells.

Scavenger receptor (SR)-specific delivery by maleylation of a ubiquitous self-protein, Ig, to SR-bearing APCs results in self-limiting induction of autoimmune effects in vivo. Immunization with maleyl-Ig breaks T cell tolerance to self-Ig and causes hypergammaglobulinemia, with increases in spleen weight and cellularity. The majority of splenic B cells show an activated phenotype upon maleyl-Ig immunization, leading to large-scale conversion to a CD138+ phenotype and to significant increases in CD138-expressing splenic plasma cells. The polyclonal B cell activation, hypergammaglobulinemia, and autoreactive Ig-specific T cell responses decline over a 2-mo period postimmunization. Following adoptive transfer, T cells from maleyl-Ig-immune mice taken at 2 wk postimmunization can induce hypergammaglobulinemia in the recipients, but those taken at 10 wk postimmunization cannot. Hypergammaglobulinemia in the adoptive transfer recipients is also transient and is followed by an inability to respond to fresh maleyl-Ig immunization, suggesting that the autoreactive Ig-specific T cells are inactivated peripherally following disruption of tolerance. Thus, although autoreactive T cell responses to a ubiquitous self-Ag, Ig, are induced by SR-mediated delivery to professional APCs in vivo resulting in autoimmune pathophysiological effects, they are effectively and rapidly turned off by inactivation of these activated Ig-specific T cells in vivo.

Animals↗
PubMed2000

Denture esophageal impaction refractory to endoscopic removal in a psychiatric patient.

Impaction of dental prostheses is frequently encountered in psychiatric patients. These patients may present an especially challenging problem because the diagnosis may be delayed, resulting in increased morbidity and mortality. Delay in diagnosis in such patients has been attributed to their inability to give a reliable clinical history. In addition, radiolucent dentures cannot be easily detected by radiographic examination. The purpose of this report is to describe a psychiatric patient with an impacted radiopaque dental prosthesis that was refractory to endoscopic intervention. An esophagotomy was needed to successfully remove the foreign body.

Dental Prosthesis↗